Service d'Hépatologie, Centre de référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Hepatology. 2012 Jul;56(1):198-208. doi: 10.1002/hep.25599. Epub 2012 Jun 5.
The development of liver fibrosis markers in primary biliary cirrhosis (PBC) is needed to facilitate the assessment of its progression and the effectiveness of new therapies. Here, we investigated the potential usefulness of transient elastography (TE) in the noninvasive evaluation of liver fibrosis stage and disease progression in PBC. We performed, first, a prospective performance analysis of TE for the diagnosis of METAVIR fibrosis stages in a diagnostic cohort of 103 patients and, second, a retrospective longitudinal analysis of repeated examinations in a monitoring cohort of 150 patients followed-up for up to 5 years. All patients were treated with ursodeoxycholic acid. Diagnostic thresholds of liver stiffness in discriminating fibrosis stages ≥ F1, ≥ F2, ≥ F3, and =F4 were 7.1, 8.8, 10.7, and 16.9 kPa, respectively. TE showed high performance and was significantly superior to biochemical markers (e.g., aspartate aminotransferase [AST]/platelet ratio, FIB-4, hyaluronic acid, AST/alanine aminotransferase ratio, and Mayo score) in diagnosing significant fibrosis, severe fibrosis, or cirrhosis. Analysis of the monitoring cohort data set using generalized linear models showed the following: (1) an overall progression rate of 0.48 ± 0.21 kPa/year (P = 0.02) and (2) no significant progression in patients with F0-F1, F2, or F3 stages, but a significant increase (4.06 ± 0.72 kPa/year; P < 0.0001) in cirrhotic patients. A cut-off value of 2.1 kPa/year was associated with an 8.4-fold increased risk of liver decompensations, liver transplantations, or deaths (P < 0.0001, Cox regression analysis).
TE is one of the best current surrogate markers of liver fibrosis in PBC. Over a 5-year period, on-treatment liver stiffness appears stable in most noncirrhotic PBC patients, whereas it significantly increases in patients with cirrhosis. Progression of liver stiffness in PBC is predictive of poor outcome.
原发性胆汁性胆管炎(PBC)肝纤维化标志物的发展有助于评估其进展和新疗法的疗效。本研究旨在探讨瞬时弹性成像(TE)在非侵入性评估 PBC 肝纤维化分期和疾病进展中的潜在作用。
首先,我们对 103 例患者的诊断队列进行了 TE 对 METAVIR 纤维化分期的前瞻性性能分析,其次,对 150 例接受熊去氧胆酸治疗并随访长达 5 年的监测队列进行了重复检查的回顾性纵向分析。
诊断阈值分别为 7.1、8.8、10.7 和 16.9 kPa,以区分纤维化分期≥F1、≥F2、≥F3 和=F4。TE 显示出较高的性能,在诊断显著纤维化、严重纤维化或肝硬化方面明显优于生化标志物(如天冬氨酸氨基转移酶[AST]/血小板比值、FIB-4、透明质酸、AST/丙氨酸氨基转移酶比值和 Mayo 评分)。使用广义线性模型对监测队列数据集进行分析显示:(1)总体进展率为 0.48±0.21 kPa/年(P=0.02);(2)F0-F1、F2 或 F3 期患者无明显进展,但肝硬化患者显著增加(4.06±0.72 kPa/年;P<0.0001)。2.1 kPa/年的临界值与肝功能失代偿、肝移植或死亡的风险增加 8.4 倍相关(P<0.0001,Cox 回归分析)。
TE 是目前 PBC 肝纤维化的最佳替代标志物之一。在 5 年的治疗期间,大多数非肝硬化 PBC 患者的肝硬度值保持稳定,而肝硬化患者的肝硬度值显著增加。PBC 患者的肝硬度进展可预测不良预后。